The costs of housing animals are a significant fraction of the cost of research. These high costs are driven by both ethical and scientific considerations, as investigators want the animals they use for research to be healthy and disease-free. The standards for the number of mice that can be housed in a cage and the frequency of cage changing, articulated in the Guide for the Care and Use of Laboratory Animals (NRC, 1996), were based on the best professional judgment, because there was an absence of good experimental data at the time. However, much has changed since the standards were established. Animal facilities have incorporated significant advances such as much cleaner animal rooms and the widespread use of pressurized individually ventilated (PIV) caging. In addition, several studies have shown that mice can be housed at densities about twice that recommended by the Guide with no adverse effects on their health or well-being, and some of these studies even show an improvement in the health and well-being of these social animals. However, some studies were short in duration, tested only one sex, measured health and well-being in a limited number of ways, and were underpowered statistically. We propose to fill these gaps in knowledge about the appropriate density for housing mice by carrying out studies that will have adequate statistical power. Include both sexes, use a wide variety of parameters to assess health and well-being, and extend over longer periods of time including one lifespan study. PUBLIC HEALTH RELEVANCE (provided by applicant): The ability to house more mice in a cage would dramatically cut the costs of animal housing, and this would benefit research into animal models of human disease by cutting costs.